Regulation and function of renal medullary cyclooxygenase-2 during high salt loading

Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE₂ is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE₂ excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Site-specific inhibition of COX-2 in the renal medulla of Sprague-Dawley rats causes sodium retention and salt-sensitive hypertension. Together, these results support the concept that renal medullary COX-2 functions an important natriuretic mediator that is activated by salt loading and its products promote sodium excretion and contribute to maintenance of sodium balance and blood pressure.